摘要
目的建立维生素A缺乏的孕鼠模型,观察孕鼠维生素A缺乏对子代鼠胚胎发育和肿瘤发生的作用。方法取Wistar雌鼠9只,12周龄,体重200-220g。将其分成2组:①维生素A缺乏饮食组6只,受孕前2周起无维生素A饮食直至产后;②正常对照组3只,给予正常饮食。所有雌鼠喂养2周后与健康Wistar公鼠交配成孕鼠。二组孕鼠产后均给予正常饮食,于哺乳期结束后立即处死。分娩后第二天每组分别随机抽取15只新生子代鼠立即处死。其余子代鼠生后给予正常饮食,至生后365d处死、解剖(如发现中途死亡,即刻解剖)。观察二组大鼠产子情况、新生子代鼠血清维生素A浓度、新生子代鼠肾发育形态、子代鼠肿瘤发生率和组织中RxRamRNA表达。结果维生素A缺乏饮食组孕鼠产子代鼠51只;正常对照组孕鼠产子代鼠44只。维生素A缺乏饮食组的新生子代鼠血清维生素A浓度为(0.51±0.13)μmol/L,明显低于对照组的新生子代鼠的血清维生素A浓度(0.81±0.15)μmol/L,P=0.000。二组新生子代鼠中均未发现肿瘤组织,但维生素A缺乏饮食组的新生鼠组织中未成熟的肾小球和。肾小管较对照组多见。维生素A缺乏组的新生子代鼠双肾中肾源性剩余检出率为60.0%,明显高于对照组(26.7%,P=0.018)。维生素A缺乏饮食组子代鼠36只,1只中途死亡,肾母细胞瘤发生率13.9%。对照组的子代鼠无肿瘤发生。维生素A缺乏饮食组子代鼠肾源性剩余检出率30.6%,明显高于对照组子代鼠肾源性剩余检出率(6.9%,P=0.001)。子代鼠中肾母细胞瘤组织的RXRamRNA表达强度为(3.17±0.15),明显低于对照组肾脏组织中RXRαmRNA表达强度(3.58±0.20),P=0.000。结论大鼠孕期维生素A缺乏会导致子代鼠。肾发育差,肾源性剩余增加,肾母细胞瘤发生率增高。维生素A可能通过上调RXRαmRNA的表达来促进肾脏分化和降低肿瘤发生。
Objective To establish the pregnant rat model of vitamin A deficiency and evaluate the effect of vitamin A deficiency on renal embryonic development and tumorigenesis in filial rats. Methods Nine female Wistar rats (aging 12 weeks, weighing 200-220 g) were divided into Vitamin A deficient Group (VAD: 6 rats were given non-vitamin-A diet from two weeks before mating and till delivery) and Normal Diet Group (ND: three rats were given normal diet). All the pregnant rats were given normal diet after delivery and were sacrificed immediately after the breastfeeding period ended. Randomly, fifteen neonate rats from each group were sacrificed on the next day after delivery. The other pups were given normal diet and sacrificed one year later. The level of serum vitamin A, morphology of kidney, incidence of tumor formation and RXRα mRNA expression in renal tissue of filial rats were assessed. Results Fifty-one and 44 neonate rats were born in VAD group and ND group respectively. The level of serum vitamin A was significantly lower in the VAD group (0. 51 ± 0. 13 μmol/L) than that in the ND group (0. 81 ± 0. 15μmol/L, P = 0. 000). No tumor was detected in either group. Significantly, more hypoplastic renal glomeruli and tubules were observed in neonates of the VAD group. The rate of nephrogenic rest (NRs) in the neonate rats in VAD group (60%) was significantly higher than that in the ND group (26. 7%, P〈0. 018). One filial rat in the VAD group died within one year. The incidence of Wilms tumor (WT) was 13.9% in the VAD group and 0% in the ND group. The rate of Nrs in the VAD group(30. 6%) was significantly higher than that in the ND group(6. 9%, P = 0. 001). The expression of RXRα mRNA in tumor tissue of the filial rats in the VAD group (3. 17 ± 0. 15) was significantly lower than that in the ND group (3.58 ± 0. 20, P = 0. 000). Conclusions Vitamin A deficiency in pregnant rats may result in renal dysplasia, increased NRs and higher incidence of WT in filial rats. Vitamin A can promote renal development and inhibit tumorigenesis, possibly by increased expression of RXRα mRNA.
出处
《中华小儿外科杂志》
CSCD
北大核心
2009年第7期476-480,共5页
Chinese Journal of Pediatric Surgery
基金
基金项目:国家自然科学基金资助项目(编号:30070780)
关键词
肾母细胞瘤
维生素A缺乏
胚胎发育
维甲类X受体a
Nephroblastoma
Vitamin A deficiency
Embryonic development
Retinoid X receptor alpha